ACS medicinal chemistry letters · 2021
BMS-813160: A Potent CCR2 and CCR5 Dual Antagonist Selected as a Clinical Candidate.
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Cherney Robert J, Anjanappa Prakash, Selvakumar Kumaravel, Batt Douglas G, Brown Gregory D, Rose Anne V, Vuppugalla Ragini, Chen Jing, Pang Jian, Xu Songmei, Yarde Melissa, Tebben Andrew J, Paidi Venkatram Reddy, Cvijic Mary Ellen, Mathur Arvind, Barrish Joel C, Mandlekar Sandhya, Zhao Qihong, Carter Percy H
Аннотация
BMS-813160 (compound 3) was identified as a potent and selective CCR2/5 dual antagonist. Compound 3 displayed good permeability at pH = 7.4 in PAMPA experiments and demonstrated excellent human liver microsome stability. Pharmacokinetic studies established that 3 had excellent oral bioavailability and exhibited low clearance in dog and cyno. Compound 3 was also studied in the mouse thioglycollate-induced peritonitis model, which confirmed its ability to inhibit the migration of inflammatory monocytes and macrophages. As a result of this profile, compound 3 was selected as a clinical candidate.